Macrolides, as an important category of anti-infection pharmaceuticals, have the advantages of excellent antibacterial activity, no anaphylactic reaction, minor side effect, and high safety. Through fifty years' development, the macrolides have become the second largest category of anti-infection pharmaceuticals, ranking only next to β-lactam antibiotics in clinical application, and occupies an important position in clinical treatment. Erythromycin, which had been widely used in the treatment of infections caused by Staphylococcus aureus, Streptococcus pneumonia, Streptococcus hemolyticus, Mycoplasma pneumonia, and the like, is one of the first generation macrolide antibiotics and is especially applicable to patients allergic to penicillin. However, the application of erythromycin is limited due to its instability in acid medium. The second generation macrolide antibiotics represented by azithromycin can solve the above problem, and are greatly improved in terms of potency and pharmacokinetics. Azithromycin (9-deoxo-9A-methyl-9A-aza-homoerythromycin A) is the first 15-membered ring marolide antibiotic discovered by Bright (U.S. Pat. No. 4,474,768) and Kobrehe (U.S. Pat. No. 4,517,367), et al. Azithromycin is a special macrolide antibiotic obtained from erythromycin through oximation, Beckmann rearrangement reaction, and introduction of a nitrogen atom into the lactone ring thereof, and subsequently reduction and methylation. Azithromycin has outstanding features including a high stability in acidic media, a good tissue penetration, a long plasma half life, a wide range of clinical applicability, a significant efficacy, and less adverse effect. In particular, azithromycin has a wider antibacterial spectrum, and has so good antibacterial activity that can inhibit gram negative bacilli, such as Haemophilus influenza, making up the insufficiency of macrolide antibiotics in the inhibition of gram negative bacilli.
Tulathromycin can be prepared by a process comprising firstly protecting the 2′-position of dihydro homoerythromycin, which is the starting material, then oxidizing and cyclizing the 4′-position thereof, removing the protecting group at the 2′-position, and subsequently aminating to form Tulathromycin in the form of salt. Tulathromycin is a newly launched macrolide semisynthetic antibiotic, which is specifically used on animals. Ministry of Agriculture of China issued a 957th announcement in 2008, first permitting the use of tulathromycin in animal production. Tulathromycin is mainly used in the treatment and prevention of swine and bovine respiratory diseases caused by Actinobacillus, Mycoplasma, Pasteurella, Haemophilus parasuis, and the like, and it has numerous advantages such as small dosage, single administration, low residue, and exclusive use on animals.
However, due to the wide use of antibiotics, in particular the continuous and improper use, drug resistance against macrolide antibiotics extensively used at present, such as azithromycin and tulathromycin, has been developed, which brings extreme difficulties to clinical treatment. In addition, acute toxicity tests have proven that tulathromycin has relatively high oral toxicity.